01: Clinical Significance of Enzymes Flashcards

1
Q

an enzyme that is generally associated with ATP regeneration in contractile or transport systems

A

Creatine kinase (CK)

  • in MUSCLE CELLS
      • involved in the storage of high energy CREATINE PHOSPHATE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

required to provide energy for the metabolic functions of the body

A
Adenosine Triphosphate (ATP)
- every contraction cycle of the muscle results in creatine phosphate use with the production of ATP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

T/F:

because of CK results are in relatively constant levels of muscle ATP

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

T/F:

the reaction catalyzed by CK is irreversible

A

FALSE

  • REVERSIBLE reaction
  • Creatine + ATP with CK —> Creatine phosphate + ADP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

tissues with the highest activities of CK

A
  • skeletal muscle
  • heart muscle
  • brain

*CK is widely distributed in tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

CK levels are frequently elevated in these disorders

A
  • MI
  • rhabdomyolysis
      • damage/breakdown in muscle cells
  • muscular dystrophy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

CK level is considered a sensitive indicator of the following disesase

A
  • ACUTE MI
  • DUCHENNE type muscular dystrophy
      • extreme elevations: 50-100x the upper limit of normal (ULN)

*CK is not entirely SPECIFIC in cardiac & skeletal muscle conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

T/F:

levels of CK does not vary with each normal individual

A

FALSE

  • levels vary with muscle mass:
      • gender = males > females
      • race = Africans higher CK
      • degree of physical conditioning = athletes have more muscle mas –> more energy required –> CK increased
      • age = older –> muscle atrophy –> lower CK
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

T/F:
the separation of total CK into its various isoenzymes is a more specific indicator of various disorders than total levels

A

TRUE

  • CK isoenzymes:
      • CK-BB (brain type)
      • CK-MM (muscle type)
      • CK-MB (muscle, brain)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

major CK isoenzyme in the sera of healthy people

A

CK-MM

  • the major isoenzyme bound in STRIATED MUSCLE & NORMAL SERUM
      • skeletal muscle contains mostly CK-MM (with small amounts of CK-MB)
      • majority of CK activity in the heart muscle is attributed to CK-MM (20% to CK-MB)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

highest concentrations of CK-BB are found in the following area/s

A
  • CNS
  • GIT
  • uterus (in pregnancy)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

condition/s associated with increased CK-MM in heart

A

MI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

condition/s associated with increased CK-MM in skeletal muscle

A
  • skeletal muscle disorder
  • muscular dystrophy
  • POLYMYOSITIS
  • hypothyroidism
  • MALIGNANT HYPERTHERMIA
  • physical activity
  • intramuscular injection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

condition/s associated with increased CK-MB in heart

A

MI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

condition/s associated with increased CK-MB in skeletal muscle

A
  • myocardial injury
  • ischemia
  • angina
  • inflammatory heart disease
  • cardiac surgery
  • Duchenne-type muscular dystrophy
  • POLYMYOSITIS
  • MALIGNANT HYPERTHERMIA
  • REYE’S SYNDROME
  • Rocky Mountain spotted fever
  • CO POISONING
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

condition/s associated with increased CK-BB in brain

A

CNS shock

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

condition/s associated with increased CK-BB in bladder

A

anoxic encephalopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

condition/s associated with increased CK-BB in lungs

A

cerebrovascular accident

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

condition/s associated with increased CK-BB in prostate

A

seizure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

condition/s associated with increased CK-BB in uterus

A

placental or uterine trauma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

condition/s associated with increased CK-BB in colon

A

carcinoma

22
Q

condition/s associated with increased CK-BB in stomach

A

REYE’S SYNDROME

23
Q

condition/s associated with increased CK-BB in thyroid

A
  • CO POISONING
  • MALIGNANT HYPERTHERMIA
  • acute & chronic renal failure
24
Q

this is the only tissue from which CK-MB enters the serum in significant quantities

A

Myocardium

  • approx. 20% of all CK-MB is in cardiac tissue
  • demonstration of >/= 6% of the total CK is considered a good indicator of myocardial damage (part. AMI)
25
Q

CK-MB course of elevation AFTER MI

A
  1. rises within 4-8h
  2. peaks at 12-24h
  3. returns to normal levels within 48-72h
26
Q

methods used for the measurement of CK isoenzymes

A
  • electrophoresis
      • reference method
      • can detect an unsatisfactory separation
      • allows visualization of interfering enzyme/s
  • ion-exchange chromatography
  • immunoassays
      • RIA
      • immunoinhibition methods
27
Q

enzyme that can interfere with the detection of CK isoenzymes

A

Adenylate kinase (AK)

  • released from RBCs in HEMOLYZED SAMPLES
  • appears as a band cathodal to CK-MM in electrophoresis
  • may also interfere with chemical or immunoinhibition methods –> falsely elevated CK or CK-MB
28
Q

sources of error in CK determination

A
  • hemolysis
      • due to AK in RBCs
      • RBCs DO NOT HAVE CK
      • interference can occur with hemolysis > 320mg/L hgb
  • serum stored in a well lit area
      • CK is inactivated by light
  • muscular activity & muscle mass
      • physically well trained = baseline levels
      • bedridden for long periods = low CK
29
Q

how does AK interfere with CK activity?

A

AK reacts with ADP to produce ATP –> ATP becomes available to participate in the reaction of CK –> false elevation

30
Q

CK reference ranges

A
  • TOTAL CK
      • males = 46-171 U/L at 37C (0.8-2.9 ukat/L)
      • females = 24-145 U/L at 37C (0.6-2.4 ukat/L)
  • CK-MB
      • < 5% of total CK
31
Q

an enzyme that catalyzes the interconversion of lactic & pyruvic acids

A

Lactate dehydrogenase (LD/LDH)

  • hydrogen-transfer enzyme
  • uses coenzyme NAD+
32
Q

areas with high concentrations of LDH

A
  • heart
  • liver
  • skeletal muscle
  • kidney
  • RBCs
  • lesser amounts found in:
      • lungs
      • smooth muscle
      • brain
33
Q

increased levels of LDH are found in the following disorders

A
  • cardiac diseases
  • hepatic diseases
  • skeletal muscle disorders
  • renal disease
  • hematologic & neoplastic disorders
34
Q

highest levels of TOTAL LDH are seen in the following

A
  • pernicious anemia

- hemolytic disorders

35
Q

course of elevation for LDH in acute MI

A
  1. rises within 12-24h
  2. peaks within 48-72h
    - - may remain elevated for 10d
36
Q

T/F:

an elevated total LDH value is a nonspecific finding

A

TRUE

  • due to the many conditions that contribute to its increase
  • there is more clinical significance when separated into 5 ISOENZYME FRACTIONS
37
Q

describe LDH isoenzymes

A
  • each comprises of 4 polypeptide chains
      • H (heart) & M (muscle)
      • MW: 32,000 Daltons each
  • 2 different polypeptide chains combine in 5 different arrangements
38
Q

identify LDH isoenzyme:

high concentrations in heart and RBCs

A

LD-1

  • HHHH
  • electrophoresis: migrates most quickly toward the anode
  • disorder associated with elevated levels in the HEART: MI
  • disorder associated with elevated levels in the RBCS: HEMOLYTIC ANEMIA
39
Q

identify LDH isoenzyme:

HHHM

A

LD-2

  • high in the heart & RBCs
  • disease associated with elevated levels in the HEART: MEGALOBLASTIC ANEMIA
  • diseases associated with elevated levels in the RBCS: ACUTE RENAL INFARCT, HEMOLYSIS

*LD-1 & LD-2 are present to approx. the same extent in tissues

40
Q

identify LDH isoenzyme:

high concentrations in the lungs, lymphocytes. spleen, and pancreas

A

LD-3

  • HHMM
  • disease associated with elevated levels in the LUNGS: PULMONARY EMBOLISM
  • disease associated with elevated levels in the SPLEEN: PULMONARY PNEUMONIA
  • diseases associated with elevated levels in the PANCREAS: CA, LYMPHOCYTOSIS
41
Q

identify LDH isoenzyme:

high concentrations are found in the liver only

A

LD-4

  • HMMM
  • disorders associated with elevated levels: HEPATIC INJURY, INFLAMMATION
42
Q

identify LDH isoenzyme:

MMMM

A

LD-5

  • high concentrations found in the SKELETAL MUSCLE only
  • electrophoresis: the slowest the migrates to the anode
  • disorder associated with elevated levels: SKELETAL MUSCLE INJURY
43
Q

major isoenzymes in the sera of healthy people

A
  1. LD-2
  2. LD-1
  3. LD-3
  4. LD-4
  5. LD-5
44
Q

T/F:

cardiac tissue & RBCs contain a higher concentration of LD-2

A

FALSE

- LD-1 is higher

45
Q

pattern that is suggestive of AMI

A

LD flipped pattern (LD-1 > LD-2)
- in cardiac necrosis & intravascular hemolysis, LD-1 levels will increase to a point at which they are present in greater concentrations than LD-2

46
Q

T/F:

LD is not specific to cardiac tissue

A

TRUE

- it is not a preferred marker for diagnosis of AMI

47
Q

an LD isoenzyme that migrates cathodic to LD-5

A

LD-6

  • alcohol dehydrogenase
  • seen in patients with ARTERIOSCLEROTIC CV FAILURE
  • appearance signifies a grave prognosis & impending death
  • may reflect liver injury secondary to severe circulatory insufficiency
      • LD-5 is elevated concurrently with the appearance of LD-6 probably representing hepatic congestion due to CVD
48
Q

sources of error for LD determination

A
  • any degree of HEMOLYSIS
      • RBCs contain an LDH conc. of approx. 100-150x that found in serum
  • temperature
      • LD activity is unstable in serum regardless of temp. at which it is stored
49
Q

if sample cannot be analyzed immediately, this should be stored at what temperature?

A

25C

- should be analyzed within 48h (or 24h)

50
Q

the most labile isoenzyme

A

LD-5

- loss of activity occurs more quickly at 4C than at 25C

51
Q

reference range of total LDH

A

125-220 U/L at 37C